JP2005509460A - Unit dose powder container - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a novel shape of a pharmaceutical container in which powder is not trapped even when a sealing member is ruptured, and a medical device and a treatment method using the container.
[Solution]
In a unit dose powder receiver comprising a brittle sealing member, the receiver inserts a powder flow channel into the sealing member such that the sealing member ruptures away from the powder. A unit dose powder receiver, characterized in that it comprises means allowing it to burst. Further, a rupturing member capable of rupturing such a unit dose powder receiver, a powder delivery device comprising the unit dose powder receiver, and a treatment method for cleaving it.

Description

  The present invention relates to a novel shape of a pharmaceutical container, and a medical device and treatment method using such a container.

  Previously known powder inhalation devices comprise a medicament contained in a blister covered by a foil. In use, both the foil and blister rupture, which causes the powdered pharmaceutical to be blown out or sucked out. However, such systems have the disadvantage that, inter alia, powdered pharmaceuticals are trapped in or around the ruptured foil or trapped in the blister space. As a result, the dose of the pharmaceutical administered to the patient may not be constant.

  U.S. Patent No. 6,057,077 discloses a blister pack containing, for example, a powdered pharmaceutical, which overcomes or mitigates the disadvantages of prior art blister packs by adjusting the diameter to depth ratio of each blister. .

  Recent developments have attempted to overcome this problem, for example, by providing a preformed cup sealed by a foil strip. In such a system, the foil strip is peeled away without being pierced or perforated to gain access to the powdered pharmaceutical. Such a system is obtained in an Accuhaler® device available from Glaxo Smith Kline, UK. However, Accuhaler, among other things, does not effectively direct the inspiratory flow to the metered powder to ensure that the powder receiver is properly emptied and the powder is transferred from the metered receiver prior to inhalation. In that respect, it still has the disadvantage of being generally inefficient.

  U.S. Pat. No. 6,053,836 to Dura comprises a rotationally mounted blister pack disc having means capable of cutting and opening a sealed blister and delivering a dose of medication to a patient. An inhaler is disclosed.

  Similarly, U.S. Pat. No. 6,057,017 to Dura discloses a dose strip for use in a powder inhaler that includes a base strip having blisters spaced apart from each other and a lid strip mounted on the base strip. doing. The lid tab is attached to the lid strip via each blister, and the peel strip is pulled away from the base strip and the lid strip, thereby cutting the lid strip open.

  While Dura's prior art document has overcome some of the problems, for example, where powdered pharmaceuticals are trapped by a ruptured foil, Dura inhalers and / or blisters are inefficient in delivering a dose of pharmaceuticals, There is a disadvantage that the amount of the retained powder is large.

  Thus, there has long been a need for an improved inhalation system that effectively emptyes the powder receiver and maximizes the efficiency of the air flow when aerosolizing the powder.

  The international application WO 01/30430 by the inventors reports, inter alia, a pharmaceutical powder cartridge system comprising a pharmaceutical holding chamber that forms a slidable fit within the sleeve.

U.S. Pat. No. 4,778,054 US Pat. No. 5,912,237 International Publication Number WO 01/72605

  As mentioned above, the main problem with prior art foil-covered receivers is that, inter alia, the foil is perforated towards the powder, which causes the powder to be trapped and blocked under or around the ruptured foil. There is an increased risk.

  The present invention comprises a foil-covered pharmaceutical powder receiver that can be ruptured by inserting (penetrating) at least one powder flow channel in intimate contact with or adjacent to the powder. A novel powder delivery system is provided. In this case, if the foil is ruptured, the foil will rupture "away from" the powder. In particular, in one aspect of the present invention, such rupture is achieved even when a member is used to rupture the foil from the outside.

  Thus, according to the present invention, in a unit dose powder receiver comprising a brittle sealing member, the receiver inserts a powder flow channel into the sealing member such that the sealing member ruptures away from the powder. A unit dose powder receiver is provided, characterized in that it comprises means allowing the brittle sealing member to rupture.

  In one particular aspect of the present invention, it is possible to hold the powder in a plane that is substantially perpendicular to the plane of the brittle sealing member.

  In one embodiment of the present invention, the unit dose powder receiver described above comprises a unit dose, for example a pharmaceutical powder, held in a powder reservoir with a powder protector. The powder protector is separate from the brittle sealing member, and preferably the powder protector is slidable so that it can be moved from a protected position to an unprotected position. In one preferred embodiment, both the powder reservoir and the powder protector are located in a plane perpendicular to the plane of the brittle sealing member. In one particularly preferred embodiment, the powder reservoir and the powder protector are, for example, those disclosed in EP 0 626 869, which is hereby incorporated by reference. Spool / spool sleeve assembly.

  In this way, the spool / spool sleeve assembly is housed within a spool receptacle, which may be frustoconical, for example. In this way, the spool / spool sleeve is positioned such that one end is located adjacent to a brittle sealing member, such as a foil, and the second end is located adjacent to the base of the receiver. Sometimes.

  The frustoconical shape of the receiver is formed such that the second end of the spool forms a slidable fit and the conical side is inclined away from the first end of the spool.

  Furthermore, the second end of the spool is located against the spigot, said spigot being separate or integral with the spool or the receptacle. The receptacle may have a recess in which the spigot sits. Preferably, the recess is such that it forms a spool sleeve and a slide. Further, the length / depth of the recess must be greater than or equal to the length of the spool sleeve. Similarly, the length of the spigot should be similar in size to the length of the spool sleeve. In this way, when the spool sleeve is urged away from the spool, the spool remains stationary and the sleeve slides into the recess, thereby exposing the spool and / or powder. Preferably, the sleeve is moved away so that the powder and / or the entire spool is exposed. In one particular aspect of the invention, at least one powder channel is in intimate contact with the powder and / or spool when the powder and / or spool is exposed.

  The size of the powder chamber varies, which allows different doses of powder to be administered. Preferably, the dimensions are determined so that the chamber is filled to provide a single desired dose. In one embodiment, the chamber is a generally elongated member, such as a cylindrical member having an open end and a closed end. If the closure member comprises a removable cap, the cap rests on the sleeve. However, preferably the open end of the chamber is provided with one or more spacers. Preferably, at least two spacers are present to allow the cap to rest uniformly. The use of spacers is preferred. This is because the spacer prevents the cap from coming into contact with the powder, and thus prevents the loss of dose accuracy. The spacer also functions to facilitate removal of the cap. The spacer may optionally include a collar on which the cap can be placed.

  The cap has the same diameter as the powder chamber. The cap may comprise a flat disc, a plug or an inverted cup. Desirably, the cap forms a closure surface that abuts the chamber and / or spacer. The length of the cap is short relative to the length of the chamber.

  The sleeve can form a sliding tool at least around the joint formed between the open end of the container and the cap. Preferably, the sleeve wraps around the entire periphery of the joint to form a seal. The sleeve is made of a substantially elastic material such as a plastic sleeve so that the inner wall of the sleeve is biased toward the joint to form a sealing engagement. In one preferred embodiment, the longitudinal sleeve is used to allow it to also function as a support for the body of the chamber. Thus, preferably, the length of the sleeve is approximately the same as the length of the chamber. In one particularly preferred embodiment, the length of the sleeve is determined so as to form the chamber and the slide with only the spacer protruding from the sleeve. When the cap is placed on the spacer and brought into contact with the chamber, the container is pushed partially through the sleeve, the closed end of the container protrudes from the sleeve, and the sleeve is in sealing engagement with the cap and container. Form a bond.

  If the closure member comprises a sealing member, preferably the sealing member is fixed to the sleeve. The sealing member generally has the same diameter as the sleeve, or optionally has a slightly larger diameter, in which case the sealing member overlaps the end of the sleeve. Preferably, the sealing member is made of any brittle material. Materials that are impermeable to moisture and / or moisture resistant are preferred. Such materials include, but are not limited to, plastic films or foils such as aluminum foil materials. In the case of a plastic sealing member, it can also be simply heat bonded to the sleeve, and in the case of a foil sealing member, a conventionally used layer of adhesive is used to bond the foil to the sleeve. Is also possible.

  The delivery device of the present invention may utilize any conventionally known means for piercing or rupturing a brittle sealing member such as a foil strip. Preferably, the bursting tool is employed to perform two functions: a function of rupturing the brittle sealing member and a function of prompting separation of the spool and the spool sleeve separately, simultaneously or sequentially. Preferably, the latter function comprises urging the spool sleeve away from the spool.

  In one further aspect of the present invention, a novel rupture member or cutting member is provided.

  In this aspect of the invention, particularly in a rupture member capable of rupturing the brittle sealing member of the unit dose powder receiver described above, the rupture member functions as a rupture member, a spool / spool holder separator and a powder channel. A rupture member is provided that is characterized in that it is possible.

  In one preferred embodiment, in order to achieve this, the rupture member is provided with one or more surfaces that can coincide with the walls of the receiver, in particular the inclined region of the receiver wall. Preferably, the inclined region of the rupturable member forms the edge of the cutting edge.

  In use, the rupture member is removed, exposing the spool and / or powder. Alternatively, the rupture member comprises one or more conduits that are capable of forming a powder passage leading from the spool to the powder delivery channel. In this way, the rupture member also comprises one or more powder channels, preferably a pair of powder channels. In one particularly preferred embodiment, the conduit can overlay all or part of the powder when the breaching member ruptures the brittle sealing member.

  The dose unit may be one of a plurality of such units arranged in series, and the unit is capable of transferring a series of metered dose powders into the inhalation passage of the dry powder inhaler. is there. When a plurality of dose units are connected together, the required sleeve consists of a cartridge with a plurality of sleeves arranged around the periphery. In such cases, the dose units themselves are connected together and together, or the sleeves are connected together and together, or both.

Thus, the present invention also provides a plurality of dose units arranged in series, each unit as described above. The units are removably or permanently attached to each other to form a chained arrangement, preferably the chains are flexible or semi-flexible. The design of the dosage unit according to the invention allows such flexibility.
A series of dose units according to this aspect of the invention is ideal for use in an inhaler. This is because this series of dose units makes it possible to sequentially supply one dose of medicine to the inhalation passage of the inhaler. This is because this series of dose units is indexed by the inhaler. If the series of dosage units is in the form of a flexible chain, the series of dosage units can be rolled up or folded down and stored compactly in an inhaler. This series of dose units may be of any suitable length. For example, the series of dose units can be supplied in a length that is longer than required for use in the inhaler but can be divided into usable lengths. In one particularly preferred embodiment, the plurality of dose units are housed in a cartridge, such a cartridge forming one further aspect of the invention.

  In use, when placed in an inhaler such as TECHNOHALER, the push rod acts on the closed end of the container protruding from the sleeve, returning the container into the sleeve and thus releasing the cap from the other end of the sleeve. . When the container is upside down, i.e. when the closed end is at the top, the cap falls and the container empties the powdered medicament in the inhalation passage of the inhaler.

  Thus, in a further feature of the present invention, a powder delivery device is provided comprising a powder dose unit as described above. In one most preferred embodiment, the powder is a pharmaceutical product, and thus preferably the delivery device is a pharmaceutical delivery device such as an inhaler, eg, a dry powder inhaler.

  Thus, in a further feature of the present invention, a dry powder inhaler is provided comprising a pharmaceutical product and a dosage unit as described above. In one further embodiment, an inhaler is provided comprising a plurality of pharmaceutical dosage units as described above.

  Where the powder delivery device comprises an inhaler, the powder channel of the rupture member comprises an air channel and / or an aerosolization channel. In general, the powder / air channel in the rupture member allows the powder to be removed from the metering member, for example in aerosolized form, while it can also be used to introduce eg wash air into the powder receiver. Is possible.

  In the inhaler of the present invention, the pharmaceutical dosage unit is preferably supplied in a cartridge as described above.

A variety of medicaments can be administered using the inhalers of the present invention. Such medicaments are generally suitable for the treatment of asthma, COPD and respiratory infections. Such medicaments include, for example, fenoterol, formoterol, pyrbutenol, reproterol, rimiterol, salbutamol, salmeterol and terbuterol. β ₂ agonists and non-selective β stimulants such as isoprenaline and xanthine bronchodilators such as theophylline, aminophylline and choline theophylline, eg ipratropium bromide Anti-cholinergic agents such as (ipratropium bromide), and mast cell stabilizers such as sodium cromoglycate and ketotifen, and nedocromil sodium such as nedocromil sodium Anti-inflammatory drugs, such as beclomethasone dipropionate, fluticasone, budesonide, flunisolide and flunisolide and flunisole And / or the like steroids such as salts or derivatives.

It is worth mentioning that certain combinations of pharmaceuticals include, for example, beclomethasone dipropionate and formoterol, beclomethasone dipropionate and salmeterol, and fluticasone. And combinations of steroids such as fluticasone and salmeterol, fluticasone and salmeterol, budesonide and formotero, budesonide and salmeterol, flunisolide and formoterol, flunisolide and salmeterol. It is within the scope of the present invention to include combinations of one or more of the aforementioned steroids with one or more of the aforementioned β ₂ agonists.

  Further useful pharmaceuticals include protein compounds and / or macromolecules such as insulin, human growth hormone, leuprolide and alpha interferon, and growth factors, anticoagulants, immunomodulators, cytokines and nucleic acids and the like Some substances become systemically active.

  In one further aspect of the invention, there is provided a powder delivery method comprising using powder delivery as described above.

  Further provided is a method for treating a patient suffering from a respiratory disorder, comprising administering a medicament using a powder delivery device as described above.

  There is also provided a method for treating a patient suffering from a systemic disease comprising administering a medicament using the powder delivery device of the present invention.

  The present invention will now be described by way of example only with reference to the accompanying drawings.

  1a-1d show a blister and a prior art drilling tool. When the foil is ruptured, it may form a folded pocket, which may trap the powder and the powder cannot escape.

  2a-2c show a prior art peelable foil blister strip. This system avoids foil strip perforation, but the efficiency of emptying the blister is limited.

  3 and 4, the unit dose powder receiver 31 comprises a spool 32 and a sleeve 33 in the form of a spool holder. Together, the spool 32 and the spool holder 33 form a pharmaceutical powder reservoir 34. The receptacle 31 comprises a cylindrical body 35 that can form a sliding tool with the sleeve 33. The cylindrical body 35 has a bottom portion 36, and one end 37 of the spool 32 includes a spigot 38, and the spigot 38 is placed on the bottom portion 36. The end 39 of the receiver 31, which is located distal to the extension 36, is provided with a recess 310. The recess 310 is recessed inward at an angle and toward the bottom 36 of the receiver 31 so that an upwardly facing inclined surface 316 is formed on either side of the receiver 31. The end 39 of the receiver 31 is provided with a sealed end face 311. The receiver 31 is provided with a foil sealing strip 312.

  During use, one end 37 of the spool 32 rests on the spigot 38 and the second end 313 of the spool 32 abuts the inner surface of the foil strip 312. The end portion 314 of the sleeve 33 also abuts the inner surface of the foil strip 312, and the sleeve 33 forms a sliding tool with the inner wall 317 of the receiver 31.

  The pharmaceutical powder 315 is accommodated between the spool 32 and the spool holder 33.

  In FIGS. 5 and 6, the assembly is similar to that previously shown in FIGS. However, the bottom 68 of the receiver 66 is provided with a spigot 69. The end 615 of the spool 62 is substantially flat and rests on the spigot 69 at the bottom of the receiver 66.

  In FIG. 7, the system includes a sealed single dose unit 721 and a foil cutting or rupturing member 722. The foil cutting member 722 includes a cylindrical body 723 and the dose unit facing the surface 724 of the cylindrical body 723 includes a pair of teeth 725 and 726. Teeth 725 and 726 are separated from each other by exactly the same dimensions as the diameter of the spool holder (not shown in FIG. 7). The inner surfaces 727 of the teeth 725 and 726 facing each other are hollow, so there is an “open” surface. The distal outer surface 728 is beveled, thereby corresponding to the beveled surface of the receiver.

  Each of the hollow teeth 725 and 726 separately form a conduit 729 that is provided on the outer wall 730 of the cylindrical body 723 and extends from the open surface 727 to the opening 720.

  In use in FIGS. 8-10, teeth 825 and 726 pierce foil strip 714 in use. The torn portion 831 of the foil 814 is biased away from the powder 818 by the inclined surfaces 828 of the teeth 825 and 826.

  The cutting edge 832 of each tooth 825 and 826 engages the upper end surface 833 of the spool holder / sleeve 83. At the same time, as the cutting member 833 further enters, the spool carrier 83 moves away from the spool 82 and slides toward the bottom 834 of the receiver 835. The spool 82 supported by the spigot 89 remains stationary.

  As the cutting member 822 further enters the receptacle, the sleeve 83 is pushed to reach the bottom 834, thereby exposing the spool 82 and the powdered medicament to the open surfaces of the teeth 825 and 826. The inclined wall 828 of the teeth 825 and 826 engages the inclined wall 836 of the receiver 835 and also presses the ruptured portion 831 of the foil against the inclined wall 836, thereby ensuring that the Any contact is eliminated.

  Air then enters through one of the conduits 837 of the teeth 825 and 826 (or alternatively, a vacuum can be utilized), which causes the drug to deagglomerate and aerosolize. , Discharged through the other conduit 838.

  The cutting member 822 is then retracted from the receiver and prepared for introducing a new filled spool.

  In FIGS. 11 a-c, a single dose unit 111 is connected together and forms a plurality of dose units in strip form 112 or cartridge form 113.

1a-1d show a prior art system for rupturing a blister using a rupture tool. 2a-2c show a prior art system for peeling a foil cover from a blister. FIG. 5 is a perspective view of a disassembled dose unit with the spool comprising an integral spigot. FIG. 3 is a cross-sectional view of a disassembled dose unit with the spool comprising an integral spigot. FIG. 3 is a perspective view of a disassembled dose unit with the receiver comprising an integral spigot. FIG. 4 is a cross-sectional view of a disassembled dose unit in which the receiver includes an integral spigot. FIG. 6 is a perspective view of a dose unit and foil cutting or rupturing tool. Figures 8a and 8b are cross-sectional views of the dose unit and a foil cutting or rupturing tool in use and rupturing the foil cover. 9a and 9b are cross-sectional views of the dose unit and the foil cutting or rupture tool used in place to deliver the pharmaceutical powder and removed after use. 10a and 10b are perspective views of the sealed dose unit before and after use. Figures 11a to 11c schematically show a single dose unit and a plurality of dose units in the form of strips and cartridges.

Claims (53)

  In a unit dose powder receiver comprising a brittle sealing member, the receiver inserts a powder flow channel into the sealing member such that the sealing member ruptures away from the powder. A unit dose powder receiver, characterized in that it comprises means allowing it to burst.   The unit dose powder receiver of claim 1, wherein the powder is held in a powder reservoir in a plane substantially perpendicular to the plane of the brittle sealing member.   2. The unit dose powder receiver of claim 1, wherein the powder is held in a powder reservoir with a powder protector.   The unit dose powder receiver of claim 3, wherein the powder reservoir and the powder protector comprise a spool / spool sleeve assembly.   5. A unit dose powder receiver according to claim 4, wherein the spool / spool sleeve assembly comprises the assembly described in European Patent Application No. 0626869.   5. The unit dose powder receiver of claim 4, wherein the spool / spool sleeve assembly is housed within a spool receiver.   6. The unit dose powder receiver of claim 5, wherein the receiver is generally frustoconical.   The spool / spool sleeve is positioned such that a first end is located adjacent to the brittle sealing member and a second end is located adjacent to the base of the receiver. A unit dose powder receiver according to claim 4.   The frustum shape of the receiver is such that the second end of the spool forms a slide with the receiver, and the conical side of the receiver is slanted away from the first end of the spool. 9. A unit dose powder receiver according to claim 8, characterized in that it is determined to do so.   The unit dose powder receiver of claim 9, wherein the second end of the spool is disposed against a spigot.   11. The unit dose powder receiver of claim 10, wherein the spigot is integral with the spool.   11. The unit dose powder receiver of claim 10, wherein the spigot is integral with the receiver.   The unit dose powder receiver of claim 10, wherein the receiver comprises a recess in which the spigot sits.   14. The unit dose powder receiver of claim 13, wherein the recess forms a slide with the spool sleeve.   15. A unit dose powder receiver according to claim 14, wherein the depth of the recess is substantially the same as the length of the spool sleeve.   The unit dose powder receiver of claim 1, wherein the dimensions are determined such that the powder reservoir is filled to provide a desired unit dose.   5. A unit dose powder receiver according to claim 4, wherein the spool and / or the spool sleeve abuts the brittle sealing member.   The unit dose powder receiver of claim 17, wherein the brittle sealing member is secured to the chamber.   2. The unit dose powder receiver of claim 1, wherein the brittle sealing member is substantially impermeable to moisture and / or moisture resistant.   The unit dose powder receiver of claim 19, wherein the brittle sealing member comprises a plastic film or foil.   21. The unit dose powder receiver of claim 20, wherein the brittle sealing member is made of an aluminum foil material.   21. The unit dose powder receiver of claim 20, wherein the brittle sealing member comprises a plastic material that is thermally bonded to the receiver.   The unit dose powder receiver of claim 21, wherein the brittle sealing member comprises a foil material bonded to the receiver by an adhesive.   The rupture member for rupturing the brittle sealing member of the unit dose powder receiver of claim 1, wherein the rupture member is capable of functioning as a rupture member, a spool / spool holder separator and a powder channel.   The rupture member according to claim 24, wherein the rupture member is capable of rupturing the brittle sealing member in a direction away from the powder.   25. The rupturable member of claim 24, wherein the rupturable member comprises one or more surfaces that can coincide with the wall of the receiver.   27. The rupture member of claim 26, wherein the rupture member comprises a pair of inclined walls that can coincide with the walls of the inclined region of the receiver.   The rupturable member according to claim 27, wherein one end of the inclined wall of the rupturable member can form a cutting edge.   30. The rupture member of claim 29, wherein the rupture member comprises one or more conduits that function as powder conduits.   30. The rupture member of claim 29, wherein the rupture member comprises a pair of powder conduits.   30. A rupture member according to claim 29, wherein the rupture member allows introduction of cleaning air into the powder receiver.   A powder delivery device comprising the unit dose powder receiver of claim 1.   The powder delivery device according to claim 32, wherein the delivery device includes a rupture means for rupturing the brittle sealing member.   34. The powder delivery device according to claim 33, wherein the rupturing means can promote separation of the spool and the spool sleeve.   35. The powder delivery device of claim 34, wherein the rupturing means is operable on the spool to slidably facilitate separation of the spool sleeve from the spool.   34. A powder delivery device according to claim 33, wherein the rupture means is capable of functioning as a powder channel.   The powder channel is located adjacent to or in close contact with the powder and / or the spool when the powder and / or the spool is exposed. Item 37. The powder delivery device according to Item 36.   37. The powder of claim 36, wherein the powder conduit of the rupture member can be overlaid on all or part of the powder when the rupture member is fully inserted. Delivery device.   2. The unit dose powder receiver of claim 1, wherein a plurality of dose units are arranged in series.   40. A cartridge comprising a series of unit dose powder receivers according to claim 39.   30. The powder delivery device of claim 29, wherein the powder is a pharmaceutical product.   42. The powder delivery device according to claim 41, wherein the delivery device is an inhaler.   43. The powder delivery device of claim 42, wherein the delivery device is a dry powder inhaler.   The powder delivery device of claim 1, wherein the powder delivery device comprises a plurality of unit dose powder receivers.   44. The powder delivery device according to claim 43, wherein the powder channel is an air channel.   42. The powder delivery device according to claim 41, wherein the powder delivery device comprises suitable indexing means. The powder, fenoterol (fenoterol), formoterol (fromoterol), and Pirubutenoru (pirbuterol), reproterol (reproterol), rimiterol (rimiterol), salbutamol (salbutamol), beta ₂ agonists such as salmeterol (salmeterol) and terbutaline (terbutaline) Non-selective β-stimulators such as isoprenaline, xanthine bronchodilators such as theophylline, aminophylline and choline theophylline, and ipratropium bromide ipratropium bromide anti-cholinergic agents such as omid), mast cell stabilizers such as sodium cromoglycate and ketotifen, and bronchial anti-inflammatory agents such as nedocromil sodium bronchial antiinflammatory agent), beclomethasone dipropionate, fluticasone, budesonide, flesolidide, and selenium With steroids, Et made, asthma, powder delivery device according to claim 41, characterized in that it is selected from the group of chemicals for the treatment of COPD or respiratory diseases.   The powder delivery device comprises beclomethasone dipropionate and formoterol, beclomethasone dipropionate and salmeterol, fluticasone and formoterol, fluticasone and A combination of steroids selected from the group consisting of salmeterol, budesonide and formotero, budesonide and salmeterol, flunisolide and formoterol, and flunisolide and salmeterol 48. The powder delivery device of claim 47.   The powder delivery device comprises protein compounds and / or macromolecules such as insulin, human growth hormone, leuprolide and alpha interferon, and growth factors, anticoagulants, immunomodulators, cytokines and nucleic acids, 42. The powder delivery device of claim 41, comprising a substance that is systemically active.   42. A powder delivery method comprising the use of the powder delivery device of claim 41.   43. A method for treating a patient with respiratory illness comprising administering a medicament using the powder delivery device of claim 42.   42. A method of treating a patient with a systemic disease comprising administering a medicament using the powder delivery device of claim 41. A unit dose powder receiver, rupture member or powder delivery device substantially the same as described with reference to the accompanying drawings.

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